Mikala Egeblad
Office: Rangos Room 452
Lab: Rangos Room 440.1
The Egeblad lab studies the contributions of the tumor microenvironment – in which cancer cells arise and live – to therapy responses and metastasis.
Solid tumors are abnormally organized tissues that contain not only cancer cells, but also various stromal cell types and extracellular matrix, and these latter components constitute the microenvironment. Communications between the different components of the tumor influence its growth, its response to therapy, and its ability to metastasize.
The lab studies the importance of tumor-stroma communications using co-culture assays and mouse models of breast and pancreatic cancer. We use co-culture assays to interrogate signaling pathways involved in communications between cancer cells and specific types of stromal cells (e.g., macrophages, neutrophils and fibroblasts). We use microscopy of tumors in live mice to determine how interactions between cancer and stromal cells or activation of specific signaling pathways influence cellular survival, proliferation and migration. We use bioluminescence and small animal ultrasound to follow tumor progression and regression at the organism level.
Our main focus is on the functions of myeloid-derived immune cells, a diverse group of cells that can enhance angiogenesis and metastasis and suppress the response to chemotherapy and the cytotoxic immune responses against tumors. We study how different types of myeloid cells are recruited to tumors and how signals between them and the cancer cells, or other immune cells, influence response to chemotherapy and metastatic spread.
Nakasone, E.S., Askautrud, H.A., Kees, T., Parks, J.-H., Plaks, V., Ewald, A.J., Fein, M., Rasch, M.G., Tan, Y.X., Qiu, J., Park, J., Sinha, P., Bissell, M., Frengen, E., Werb, Z., and Egeblad, M. (2012). Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell, 21, 488-503
Park, J., Wysocki, R.W., Amoozgar, Z., Maiorino, L., Fein, M.R., Jorns, J., Schott, A.F., Kinugasa-Katayama, Y., Lee, Y., Won, N.H., Nakasone, E.S., Hearn, S.A., Küttner, V., Qiu, J., Almeida, A.S., Perurena, N., Kessenbrock, K., Goldberg, M.S., and Egeblad, M. (2016). Cancer cells trigger neutrophils to induce metastasis-supporting extracellular DNA traps. Sci Transl Med, 8, 361ra138
Albrengues, J., Shields, M.A., Ng, D., Park, C.G., Ambrico, A., Poindexter, M., Upadhyay, P., Uyeminami, D., Pommier, A., Küttner, V., Bružas, E., Maiorino, L., Bautista, C., Carmona, E.M., Gimotty, P.A., Fearon, D.T., Chang, K., Lyons, S.K., Pinkerton, K., Trotman, L.C., Goldberg, M.S., Yeh, J.T.-H., and Egeblad, M. (2018). Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science, 361, 6409. pii: eaao4227. doi: 10.1126/science.aao4227
Middleton, E.A., He, X.-Y., Denorme, F., Campbell, R.A., Ng, D., Salvatore, S.P., Mostyka, M., Baxter-Stoltzfus, A., Borczuk, A.C., Loda, M., Cody, M.J., Manne, B.K., Portier, I., Harris, E.S., Petrey, A.C., Beswick, E.J., Caulin, A.F., Lovino, A., Abegglen, L.M., Weyrich, A.S., Rondina, M.T., Egeblad, M., Schiffman, J.D., and Yost, C.C. (2020). Neutrophil extracellular traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood, 136:1169-1179. doi.org/10.1182/blood.2020007008
Fein, M.R., He, X.-Y., Almeida, A.S., Bružas, E., Pommier, A., Yan, R., Eberhardt, A., Fearon, D.T., Van Aelst L., Wilkinson, J.E., dos Santos, C.O., and Egeblad, M. (2018). Cancer cell CCR2 orchestrates suppression of the adaptive immune response. J Exp Med, 217: e20181551. doi: 10.1084/jem.20181551
Sun L., Kees T., Almeida A.S., Liu B., He X.Y., Ng D., Han X., Spector D.L., McNeish I.A., Gimotty P., Adams S., and Egeblad M. (2021) Activating a collaborative innate-adaptive immune response to control breast and ovarian cancer metastasis. Cancer Cell, 39, 1361-1374. Selected for the cover
Adrover, J.M., Carrau, L., Daßler-Plenker, J., Bram, Y., Chandar, V., Houghton, S., Redmond, D., Merrill, J.R., Shevik, M., tenOever, B.R., Lyons, S.K., Schwartz, R.E., and Egeblad, M. (2022) Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection. JCI Insight, 7: e157342. https://doi.org/10.1172/jci.insight.157342. Selected for the cover.
Egeblad, M. and Werb, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2, 161-174
Egeblad, M., Nakasone, E.S., and Werb, Z. (2010). The tumor as an organ: complex tissues that interface with the entire organism. Dev Cell, 18, 884-901
Barnes, B.J., Adrover, J.M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J.M., Daßler-Plenker, J., Guerci, P., Huynh, C., Knight, J.S., Loda, M., Looney, M.R., McAllister, F., Rayes, R., Renaud, S., Rousseau, S., Salvatore, S., Schwartz, R.E., Spicer, J., Yost, C.C., Weber, A., Zuo, Y., and Egeblad, M. (2020). Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med, 217(6):e20200652. doi: 10.1084/jem.20200652
Maiorino, L., Daßler-Plenker, J., Sun, L, and Egeblad, M. Innate Immunity and Cancer Pathophysiology (2022) Annu Rev Pathol. doi: 10.1146/annurev-pathmechdis-032221-115501
Quail, D.F., Amulic, B., Aziz, M., Barnes, B.J., Eruslanov, E., Fridlender, Z.G., Goodridge, H.S., Granot, Z., Hidalgo, A., Huttenlocher, A., Kaplan, M.J., Malanchi, I., Merghoub, T., Meylan, E., Mittal, V., Pittet, M.J., Rubio-Ponce, A., Udalova, I.A., van den Berg, T.K., Wagner, D.D., Wang., P., Zychlinsky, A., de Visser, K.E., Egeblad, M., Kubes, P. (2022) Neutrophil phenotypes and functions in cancer: a consensus statement. J Exp Med, 219(6):e20220011. doi: 10.1084/jem.20220011
Adrover JM, McDowell SAC, He XY, Quail DF, Egeblad M. (2023) NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps. Cancer Cell, S1535-6108(23)00011-9. doi: 10.1016/j.ccell.2023.02.001